Avamina

Package leaflet: Information for the patient

AVAMINA, 500 mg, film-coated tablets
AVAMINA, 850 mg, film-coated tablets
AVAMINA, 1000 mg, film-coated tablets
Metformini hydrochloridum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary. If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Avamina is and what it is used for
2. What you need to know before taking Avamina
3. How to take Avamina
4. Possible side effects
5. How to store Avamina
6. Contents of the pack and other information

1. What Avamina is and what it is used for

Avamina contains metformin, an active substance used in the treatment of diabetes. It belongs to a group of medicines called biguanides.
Insulin is a hormone produced by the pancreas that enables the body to take up glucose (sugar) from the blood. The body uses glucose to produce energy or stores it for later use.
In people with diabetes, the pancreas does not produce enough insulin or the body cannot properly use the insulin it produces. This leads to abnormally high levels of glucose in the blood. Avamina helps reduce blood glucose levels to values as close as possible to normal.
In overweight adults, long-term use of Avamina also reduces the risk of diabetes-related complications. Treatment with Avamina is associated with maintenance of body weight or even moderate weight reduction.
Avamina is used to treat patients with type 2 diabetes (also known as non-insulin-dependent diabetes) in whom adequate control of blood glucose levels cannot be achieved by diet and physical exercise alone. It is particularly used in overweight patients.
Adults may take Avamina either as monotherapy or in combination with other antidiabetic medicines (oral agents or insulin).
Children aged 10 years and adolescents may take Avamina either as monotherapy or in combination with insulin.

2. Important information before using Avamina

When not to use Avamina

• if the patient has a known allergy (hypersensitivity) to metformin or any of the other ingredients of Avamina (listed in section 6),
• in case of liver dysfunction,
• if the patient has significantly reduced kidney function,
• if the patient has uncontrolled diabetes, for example severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, sudden weight loss, lactic acidosis (see "Risk of lactic acidosis" below) or ketoacidosis. Ketoacidosis is a condition in which substances called ketone bodies accumulate in the blood, potentially leading to a diabetic pre-coma state. Symptoms include abdominal pain, rapid and deep breathing, drowsiness, or an unusual fruity odour of the breath.
• in case of excessive fluid loss (dehydration), for example due to prolonged or severe diarrhoea or repeated vomiting. Dehydration may lead to kidney dysfunction, which may increase the risk of lactic acidosis (see section "Warnings and precautions" below).
• in case of severe infection, for example pneumonia, bronchitis or kidney infection. Severe infections may lead to kidney dysfunction, which may increase the risk of lactic acidosis (see section "Warnings and precautions" below).
• in case of treatment for acute heart failure or recent heart attack, severe circulatory disorders (e.g. shock) or breathing difficulties. These conditions may cause tissue hypoxia, which may increase the risk of lactic acidosis (see section "Warnings and precautions" below).
• in case of alcohol abuse.

If any of the above situations apply, the patient should consult a doctor before using this medicine.
It is essential to consult a doctor if:

• a radiological examination or a procedure requiring intravenous administration of an iodine-containing contrast agent is required,
• a major surgical procedure is planned.

Avamina must be discontinued for a certain period before and after such examination or surgery.
The doctor will decide whether alternative treatment is necessary during this time. It is important to
follow the doctor's instructions precisely.

Warnings and precautions
Risk of lactic acidosis
Avamina may cause a very rare but serious adverse effect called lactic acidosis, especially if the patient has kidney dysfunction. The risk of lactic acidosis increases in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more detailed information below), liver dysfunction, and any medical conditions in which a part of the body is inadequately supplied with oxygen (e.g. acute severe heart disease).
If any of the above conditions apply to the patient, the patient should consult the doctor for further instructions.

Avamina should be temporarily discontinued if the patient develops a medical condition that may lead to dehydration (significant loss of body water), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient is drinking less fluid than usual. The patient should consult the doctor for further instructions.

Avamina must be discontinued and the patient should contact a doctor or the nearest hospital immediately if any symptoms of lactic acidosis occur, as this condition may lead to coma.
Symptoms of lactic acidosis include:

• vomiting,
• abdominal pain,
• muscle cramps,
• general malaise accompanied by profound fatigue,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring immediate hospital treatment.
The patient should contact a doctor immediately for further instructions if:

• the patient has a genetically inherited mitochondrial disorder (cellular energy-producing structures), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD),
• after starting metformin, the patient experiences any of the following symptoms: seizures, worsening cognitive function, difficulty moving, symptoms indicating nerve damage (e.g. pain or numbness), migraine or deafness.

If the patient is scheduled for a major surgical procedure, Avamina must not be used during the procedure and for some time afterwards. The doctor will decide when the patient should stop and restart treatment with Avamina.

Avamina does not cause hypoglycaemia (low blood glucose levels). However, if Avamina is used in combination with other antidiabetic medicines that may cause hypoglycaemia, such as sulfonylureas, insulin or meglitinides, there is a risk of hypoglycaemia.
If symptoms of hypoglycaemia occur, such as weakness, dizziness, increased sweating, rapid heartbeat, blurred vision or difficulty concentrating, consuming food or a sugary drink usually helps.

During treatment with Avamina, the doctor will monitor kidney function at least once a year, or more frequently if the patient is elderly and/or has worsening kidney function.

Avamina and other medicines
If the patient is to receive an intravenous iodine-containing contrast agent, for example during an X-ray examination or computed tomography, the patient must stop taking Avamina before or at the latest at the time of administration. The doctor will decide when the patient should stop and restart treatment with Avamina.

The patient should inform the doctor about all medicines currently used, recently used, or planned for use. The patient may require more frequent monitoring of blood glucose levels and kidney function, or the doctor may need to adjust the dose of Avamina. It is especially important to inform the doctor about the following medicines:

• diuretics (medicines that increase urine production),
• medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib),
• certain medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists),
• beta-2 adrenergic receptor agonists, such as salbutamol and terbutaline used in the treatment of asthma,
• corticosteroids used to treat various conditions, such as severe skin inflammation or asthma,
• medicines that may alter the blood concentration of Avamina, especially if the patient has impaired kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib),
• other medicines used to treat diabetes.

Avamina and alcohol
The patient should avoid consuming excessive amounts of alcohol while taking Avamina, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding
If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should discuss with her doctor whether any changes in treatment or monitoring of blood glucose levels are necessary.
This medicine is not recommended for patients who are breastfeeding or planning to breastfeed.

Driving and operating machinery
Avamina does not cause hypoglycaemia (low blood glucose levels). This means it does not affect the patient's ability to drive or operate machinery.
However, caution is advised if Avamina is used together with other antidiabetic medicines that may cause hypoglycaemia (such as sulfonylureas, insulin and meglitinides). Symptoms of hypoglycaemia include weakness, dizziness, increased sweating, rapid heartbeat, blurred vision or difficulty concentrating. If such symptoms occur, the patient should not drive or operate machinery.

3. How to use Avamina

This medicine should always be taken exactly as directed by your doctor. If in doubt, consult your
doctor or pharmacist.
Avamina does not replace the benefits of a healthy lifestyle. You should continue to follow all
your doctor's advice regarding diet and regular physical activity.
Recommended dose
Children aged 10 years and adolescents usually start treatment with a dose of 500 mg or 850 mg of
Avamina once daily. The maximum daily dose is 2000 mg, taken in 2 or 3 divided doses. Treatment
in children aged 10 to 12 years should only be initiated on special medical advice, as experience
with Avamina in this age group is limited.
Adults usually start treatment with a dose of 500 mg or 850 mg of Avamina 2 or 3 times daily.
The maximum daily dose is 3000 mg, administered in 3 divided doses.
Patients with impaired renal function
If a patient has impaired kidney function, the doctor may prescribe a lower dose.
If a patient is also using insulin, the doctor will advise on how to start treatment with Avamina.
Monitoring of treatment

• Your doctor will order regular blood glucose tests and adjust the dose of Avamina according to blood glucose levels. You should attend regular follow-up visits with your doctor. This is particularly important for children, adolescents, and elderly patients.
• Your doctor will check kidney function at least once a year. More frequent monitoring may be necessary for elderly patients or if the patient's kidneys are not functioning properly.

How to take Avamina
Avamina should be taken during or immediately after a meal. This helps to avoid gastrointestinal
side effects.
Do not crush or chew the tablets. Swallow the tablets whole with a glass of water.

• If taking one dose per day, take the medicine in the morning (with breakfast).
• If taking two doses per day, take them in the morning (with breakfast) and in the evening (with dinner).
• If taking three doses per day, take them in the morning (with breakfast), at midday (with lunch), and in the evening (with dinner).

If, after some time, the patient feels that the effect of Avamina is too strong or too weak, they should
consult their doctor or pharmacist.
Taking more Avamina than recommended
If more Avamina is taken than recommended, lactic acidosis may occur. Symptoms of lactic
acidosis are non-specific and include vomiting, abdominal pain with muscle cramps, general
malaise accompanied by severe fatigue, and difficulty breathing. Other symptoms include lowered
body temperature and slowed heart rate.
If any of these symptoms occur, the patient should seek immediate medical help,
because lactic acidosis can lead to coma. Avamina should be stopped immediately and the
patient should contact their doctor or go to the nearest hospital.
(see section "Warnings and precautions").
Missed dose of Avamina
Do not take a double dose to make up for a missed dose. Take the next dose at the usual time.
If you have any further doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, Avamina may cause adverse reactions, although not everyone experiences them. The possible adverse reactions are listed below.

Avamina very rarely (may occur in up to 1 in 10,000 patients) may cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If lactic acidosis occurs in a patient, treatment with Avamina must be discontinued immediately and the patient should contact a doctor or the nearest hospital without delay, as lactic acidosis may lead to coma.

Very common adverse reactions (occur in more than 1 in 10 patients):

• Gastrointestinal disturbances such as nausea, vomiting, diarrhoea, abdominal pain (pain in the abdominal cavity), and loss of appetite. These adverse reactions most commonly occur at the beginning of Avamina treatment. It may help to divide the daily dose into several smaller doses taken throughout the day and to take Avamina with food or immediately after a meal. If symptoms do not resolve, Avamina should be discontinued and the doctor informed.

Common adverse reactions (may occur in less than 1 in 10 patients):

• Taste disturbances.
• Reduced or low blood levels of vitamin B (symptoms may include extreme fatigue, pain and redness of the tongue (glossitis), sensations of tingling (paraesthesia), or pale or yellowish skin). The doctor may order several tests to determine the cause of symptoms, as some of them may also be caused by diabetes or other health problems unrelated to diabetes.

Very rare adverse reactions (occur in less than 1 in 10,000 patients):

• Lactic acidosis. This is a very rare but serious complication, particularly when kidneys are not functioning properly. Symptoms of lactic acidosis are non-specific (see section "Warnings and precautions").
• Abnormal liver function test results or symptoms of hepatitis (associated with fatigue, loss of appetite, weight loss, and with or without yellowing of the skin and whites of the eyes). If such symptoms occur, Avamina should be discontinued and the doctor informed.
• Skin reactions such as skin redness (erythema), itching, or itchy rash (urticaria).

Children and adolescents
Limited data from studies in children and adolescents indicate that adverse reactions observed in these populations are of similar nature and severity to those observed in adults.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw;
Tel.: +48 22 49 21 301;
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Avamina

Keep this medicine out of sight and reach of children.
If Avamina is being used in a child, parental or caregiver supervision is recommended.
There are no special storage instructions for this medicine.
Do not use Avamina after the expiry date stated on the carton or blister pack following the label "EXP". The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Other information

What Avamina contains
The active substance in Avamina is metformin in the form of metformin hydrochloride (Metformini hydrochloridum).
Avamina 500 mg: One coated tablet contains 500 mg of metformin hydrochloride, equivalent to 390 mg of metformin.
Avamina 850 mg: One coated tablet contains 850 mg of metformin hydrochloride, equivalent to 663 mg of metformin.
Avamina 1000 mg: One coated tablet contains 1000 mg of metformin hydrochloride, equivalent to 780 mg of metformin.

Other components of the medicine are:
Tablet core: povidone K-90, magnesium stearate
Coating: hypromellose 5cP, macrogol 400 and macrogol 6000.

What Avamina looks like and contents of the pack
Coated tablet.
Avamina 500 mg
White, round, biconvex coated tablets engraved with the letter "A" on one side and the digits "60" on the other.
Avamina 850 mg
White, round, biconvex coated tablets imprinted with the letter "A" on one side and the digits "61" on the other.
Avamina 1000 mg
White, capsule-shaped, biconvex coated tablets with a central dividing line on one side and imprinted with the letter "A" and digits "90" on the other side, separated by the dividing line.
The tablet can be divided into two equal doses.

Avamina is available in blister packs.
Each carton contains 30, 60, 90 or 120 coated tablets in blisters of 10 coated tablets each.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
BIOTON S.A.
ul. Starościńska 5
02-516 Warszawa